Wang R.,Jiangsu Simcere Pharmaceutical R and D Co. |
Wang G.-J.,China Pharmaceutical University |
Wu X.-L.,China Pharmaceutical University |
Zhou F.,China Pharmaceutical University |
Li Y.-N.,China Pharmaceutical University
Chinese Journal of Natural Medicines
Aim: Although ginsenoside Rg1 possesses potent neuroprotective effects, it cannot easily be transported to brain parenchyma because of the blood-brain barrier (BBB). This study was aimed to verify the hypothesis that the ginsenoside Rg1 neuroprotective effect might be mainly derived from its direct protective effects on BBB. Methods: Male Sprague-Dawley rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) by using the suture insertion method followed by 22 h of reperfusion. In the Rg1-treated group, Rg1 (45 mg·kg-1) was administrated via tail venous (i.v.) 1 h before focal ischemia and 3 h after reperfusion. The integrity of the BBB was measured in vivo, MDA and SOD were estimated in vitro. The expression and activity of matrix metalloproteinases (MMPs), and the expression of tissue inhibitor of matrix metalloproteinases (TIMPs) mRNA, were determined to evaluate the protective effect of Rg1 on BBB structure both in vivo and in vitro. Results: In ischemia/reperfusion rats, using the EB dye extravasation, the expression and activity of MMPs were increased as compared to sham rats, while in Rg1-treated rats, these increases were inhibited. The expression of TIMP-2 mRNA in the ischemia/reperfusion rats was decreased as compared to sham rats, while in Rg1-treated rats, these decreases were ameliorated. The results of in vitro models were consistent with those of in vivo models. Conclusion: Ginsenoside Rg1 may exert its protective effect of CNS indirectly by protecting the structure of the BBB, through protecting BMECs and reducing the expression and activity of MMPs in pathological conditions. © 2013 China Pharmaceutical University. Source
Yang H.,Nanjing University |
Zhang H.,Nanjing University |
Zhu L.,Jiangsu Simcere Pharmaceutical R and D Co. |
Wang J.,Nanjing University |
And 2 more authors.
International Journal of Oncology
Carcinogenesis is a multi-step process, which includes oncogene activation, mutation silencing of tumor suppressor genes, impairment of chromosomes or epigenetic changes such as CpG island methylation through various cellular pathways, involving a series of somatic genetic alterations. Furthermore, miRNAs present a mechanism by which genes with diverse functions on multiple pathways can be simultaneously regulated at the post-transcriptional level. However, little is known about the cancer-related pathways through which cancer-associated miRNAs (CA-miRNAs) regulate these processes representing either positive or negative functions in carcinogenesis. This study investigated eleven miRNAs previously identified cancer-related regulators. Using function and pathway analysis of their targeted genes, the relevance of miRNA regulation the induction of cancer can be observed. The results showed that CA-miRNAs may function in the post-transcriptional level mainly through manipulating the expression of transcription factors and protein kinases, and target genes for the CA-miRNAs were most prominently predicted to function the regulation of transcription. Our analysis also highlighted the potential of these CA-miRNAs to regulate the cell differentiation, proliferation, endocytosis and migration signaling logically required to cause a cancer cell mainly through five canonical pathways. Combined with previous cancer studies, the analysis of the relevance between functions of CA-miRNAs and cancer-related pathways exploring different internal carcinogenesis stimuli also revealed the potential of the top five pathways to regulate core carcinogenesis processes. These findings should form a useful knowledge base for potential future development of novel therapeutic treatments. Source
Yu S.,Jiangsu Simcere Pharmaceutical R and D Co. |
Yu Y.,China Pharmaceutical University |
Liu L.,China Pharmaceutical University |
Wang X.,China Pharmaceutical University |
And 5 more authors.
Our previous study showed a higher exposure of berberine, palmatine, coptisine, epiberberine and jatrorrhizine in 6-week streptozotocin (STZ)-induced diabetic rats, after oral administration of Coptidis Rhizoma extract. The aim of the present study was to investigate whether the function and expression of intestinal P-glycoprotein (PGP) was downregulated in STZ-induced diabetic rats and if the impairment of PGP function and expression contributed to the exposure increase of the five protoberberine alkaloids. Plasma concentration-time profiles of the drugs in the portal vein were obtained after oral administration of Coptidis Rhizoma extract. The effective permeability of the drug across duodenum and ileum were measured using in situ single-pass intestine perfusion. PGP function in the rat intestine was assessed by measuring the absorption of rhodamine 123 (Rho123). PGP levels were evaluated using Western blots. It was found that the Cmax and AUC0-8 values of five alkaloids in the portal vein of diabetic rats were significantly higher than those in the control rats. Diabetic rats also exhibitd a higher level of Rho123 in the portal vein, which showed impairment of PGP function. A higher effective permeability of the tested drug was found in the duodenum of diabetic rats using in situ single-pass intestine perfusion, indicating that berberine and Rho123 transported more easily across the intestinal barrier of diabetic rats. A lower level of PGP protein was found in the duodenum, jejunum and ileum of the diabetic rats as compared with age-matched control rats. All these results suggested that the function and expression of PGP were impaired in the intestine of STZ-induced diabetic rats which, at least partly, contributed to the exposure increase of the five protoberberine alkaloids. © Georg Thieme Verlag KG Stuttgart New York•. Source
Huang W.,Jiangsu Simcere Pharmaceutical R and D Co. |
Huang W.,Nanjing University |
Tan A.,Jiangsu Simcere Pharmaceutical R and D Co.
Acta Crystallographica Section E: Structure Reports Online
In the title compound, C15H12FN3O 3·CH3OH, the dihedral angle between the quinazoline ring system and the benzene ring is 81.18 (9)°. In the crystal, mol-ecules are linked by N-H⋯O and O-H⋯N hydrogen bonds, generating [10-1] chains of alternating main mol-ecules and solvent mol-ecules. Weak C-H⋯O inter-actions are also observed. Source
Fu Z.,Macau University of Science and Technology |
Fu Z.,Jiangsu Simcere Pharmaceutical R and D Co. |
Chen X.,Nanjing University |
Guan S.,Nanjing University |
And 5 more authors.
Curcumin, a natural polyphenol compound from the perennial herb Curcuma longa, has been proved to be beneficial for tumor-bearing animals through inhibiting tumor neovasculature formation, but the underlying mechanisms are unclear. Here, we aim to test whether curcumin affects VEGF-VEGFR2 signaling pathway and attenuates defective hematopoiesis induced by VEGF in tumor model. We demonstrated that curcumin inhibited proliferation, migration of HUVEC under VEGF stimulation and caused HUVEC apoptosis, and blocked VEGFR2 activation and its downstream signaling pathways in vitro. Furthermore, in VEGF over-expressing tumor model, curcumin significantly inhibited the tumor growth accelerated by VEGF in a dose-dependent manner and improved anemia and extramedullary hematopoiesis in livers and spleens of tumor-bearing mice induced by tumor-derived VEGF. Immunohistochemical analysis showed that curcumin normalized vasculature structures of livers and reduced tumor microvessel density. ELISA revealed that curcumin suppressed VEGF secretion from tumor cells both in vitro and in vivo. Survival analysis showed that curcumin significantly improved survival ability of VEGF tumor-bearing mice. Taken together, these findings establish curcumin as a modulator of VEGF and VEGF-VEGFR2 signaling pathway, with potential implication for improving the quality of life of cancer patients. Source